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Showing papers by "Eugene Braunwald published in 2020"


Journal ArticleDOI
TL;DR: It is critical for cardiologists, diabetologists, nephrologists, and primary care physicians to be familiar with SGLT2i, as their use is now being studied in the treatment of heart failure and chronic kidney disease, even in patients without diabetes.

262 citations


Journal ArticleDOI
TL;DR: The term atrial failure is proposed as a clinically relevant entity, defined as any atrial dysfunction causing impaired heart performance, symptoms, and worsening quality of life or life expectancy.

154 citations


Journal ArticleDOI
TL;DR: In patients aged 75 years and older, lipid lowering was as effective in reducing cardiovascular events as it was in patients younger than 75 years, and guideline recommendations for the use of lipid-lowering therapies, including non-statin treatment, in older patients should strengthen.

128 citations


Journal Article
TL;DR: It is shown that hyaluronidase can accelerate the reduction of myocardial ischemic injury in patients with acuteMyocardial infarction.
Abstract: The effect of hyaluronidase on myocardial ischemic injury was examined in 13 patients with acute myocardial infarction, and the results were compared with 11 patients who did not receive h...

86 citations


Journal ArticleDOI
TL;DR: The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome.
Abstract: Author(s): Anker, Stefan D; Butler, Javed; Khan, Muhammad Shahzeb; Abraham, William T; Bauersachs, Johann; Bocchi, Edimar; Bozkurt, Biykem; Braunwald, Eugene; Chopra, Vijay K; Cleland, John G; Ezekowitz, Justin; Filippatos, Gerasimos; Friede, Tim; Hernandez, Adrian F; Lam, Carolyn SP; Lindenfeld, JoAnn; McMurray, John JV; Mehra, Mandeep; Metra, Marco; Packer, Milton; Pieske, Burkert; Pocock, Stuart J; Ponikowski, Piotr; Rosano, Giuseppe MC; Teerlink, John R; Tsutsui, Hiroyuki; Van Veldhuisen, Dirk J; Verma, Subodh; Voors, Adriaan A; Wittes, Janet; Zannad, Faiez; Zhang, Jian; Seferovic, Petar; Coats, Andrew JS | Abstract: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infection with COVID-19 and the consequences might also be more serious, but they are also at risk of adverse outcomes if their clinical care is compromised. As physicians and clinical trialists, it is our responsibility to ensure safe and effective care is delivered to trial participants without affecting the integrity of the trial. The social contract with our patients demands no less. Many regulatory authorities from different world regions have issued guidance statements regarding the conduct of clinical trials during this COVID-19 crisis. However, international trials may benefit from expert guidance from a global panel of experts to supplement local advice and regulations, thereby enhancing the safety of participants and the integrity of the trial. Accordingly, the Heart Failure Association of the European Society of Cardiology on 21 and 22 March 2020 conducted web-based meetings with expert clinical trialists in Europe, North America, South America, Australia, and Asia. The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome, with some practical examples. While this panel of experts are focused on heart failure clinical trials, these discussions and recommendations may apply to clinical trials in other therapeutic areas.

66 citations


Journal ArticleDOI
TL;DR: This second part of this 2-part review summarizes the findings of recent clinical trials and their clinical implications and describes ongoing trials and future areas of research.

62 citations


Journal ArticleDOI
TL;DR: Switching patients' treatment from enalapril to sacubitril/valsartan at 8 weeks after randomization led to a further 37% reduction in NT-proBNP levels in patients with heart failure with reduced ejection fraction and a recent hospitalization for ADHF.
Abstract: Importance In PIONEER-HF, among stabilized patients with acute decompensated heart failure (ADHF), the in-hospital initiation of sacubitril/valsartan was well tolerated and led to improved outcomes compared with enalapril. However, there are limited data comparing the strategies of in-hospital vs postdischarge initiation of sacubitril/valsartan. Objective To describe changes in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels in patients recently hospitalized for ADHF and switching from taking enalapril to taking sacubitril/valsartan after discharge and compare clinical outcomes for patients randomized to receive in-hospital initiation of sacubitril/valsartan vs in-hospital initiation of enalapril who later switched to taking sacubitril/valsartan during an open-label extension phase. Interventions Sacubitril/valsartan titrated to 97/103 mg twice daily. Design, Setting, and Participants The PIONEER-HF trial was a multicenter, randomized, double-blind, active-controlled trial conducted at 129 US sites between May 2016 and May 2018 that compared the in-hospital initiation of sacubitril/valsartan vs enalapril (titrated to target dose, 10 mg twice daily) for 8 weeks among patients admitted for ADHF with reduced ejection fraction and hemodynamic stability. All patients were to continue in a 4-week, open-label study of sacubitril/valsartan; of 881 patients enrolled in PIONEER-HF, 832 (94%) continued in the open-label study. Main Outcomes and Measures Changes in NT-proBNP levels from week 8 to 12 as well as the exploratory composite of heart failure rehospitalization or cardiovascular death from randomization through week 12. Results Of 881 participants, 226 (27.7%) were women, 487 (58.5%) were white, 297 (35.7%) were black, 15 (1.8%) were Asian, and 73 (8.8%) were of Hispanic ethnicity; the mean (SD) age was 61 (14) years. For patients who continued to take sacubitril/valsartan, NT-proBNP levels declined −17.2% (95% CI, −3.2 to −29.1) from week 8 to 12. The NT-proBNP levels declined to a greater extent for those switching from taking enalapril to sacubitril/valsartan after the week 8 visit (−37.4%; 95% CI, −28.1 to −45.6;P Conclusions and Relevance Switching patients’ treatment from enalapril to sacubitril/valsartan at 8 weeks after randomization led to a further 37% reduction in NT-proBNP levels in patients with heart failure with reduced ejection fraction and a recent hospitalization for ADHF. Trial Registration ClinicalTrials.gov identifier:NCT02554890.

52 citations


Journal ArticleDOI
L. Christian Napp1, Victoria L. Cammann2, Miłosz Jaguszewski3, Konrad A. Szawan2, Manfred Wischnewsky4, Sebastiano Gili, Maike Knorr, Susanne Heiner, Rodolfo Citro, Eduardo Bossone, Fabrizio D'Ascenzo5, Michael Neuhaus, Jennifer Franke6, Ioana Sorici-Barb6, Michel Noutsias7, Christof Burgdorf, Wolfgang Koenig8, Behrouz Kherad9, Annahita Sarcon10, Lawrence Rajan11, Guido Michels12, Roman Pfister12, Alessandro Cuneo, Claudius Jacobshagen13, Mahir Karakas, Alexander Pott14, Philippe Meyer, Jose David Arroja, Adrian P. Banning15, Florim Cuculi, Richard Kobza, Thomas Fischer16, Tuija Vasankari17, K.E. Juhani Airaksinen17, Christian Hauck18, Carla Paolini, Claudio Bilato, Yoichi Imori19, Ken Kato20, Yoshio Kobayashi20, Grzegorz Opolski21, Monika Budnik21, Rafal Dworakowski22, Philip MacCarthy22, Christoph Kaiser23, Stefan Osswald23, Leonarda Galiuto24, Wolfgang Dichtl, Christina Chan25, Paul Bridgman25, Daniel Beug26, Clément Delmas, Olivier Lairez, Ibrahim El-Battrawy27, Ibrahim Akin27, Ekaterina Gilyarova, Alexandra Shilova, Mikhail Gilyarov, John D. Horowitz28, Karolina Polednikova29, Petr Tousek29, Petr Widimský29, David E. Winchester30, Jan Galuszka, Christian Ukena, Gregor Poglajen, Pedro Carrilho-Ferreira31, Carlo Di Mario, Abhiram Prasad32, Charanjit S. Rihal32, P. Christian Schulze33, Matteo Bianco, Filippo Crea24, Martin Borggrefe27, Lars S. Maier18, Fausto J. Pinto31, Ruediger C. Braun-Dullaeus34, Wolfgang Rottbauer14, Hugo A. Katus6, Gerd Hasenfuß13, Carsten Tschöpe9, Burkert Pieske9, Holger Thiele35, Heribert Schunkert8, Michael Böhm, Stephan B. Felix26, Thomas Münzel, Jeroen J. Bax36, Johann Bauersachs1, Eugene Braunwald37, Thomas F. Lüscher38, Thomas F. Lüscher2, Frank Ruschitzka2, Jelena R. Ghadri2, Christian Templin2 
TL;DR: Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome.
Abstract: AIMS Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS. METHODS AND RESULTS Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort. CONCLUSIONS Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome. TRIAL REGISTRATION ClinicalTrials.gov number: NCT01947621.

48 citations


Journal ArticleDOI
TL;DR: For patients with HFrEF, initiation of sacubitril-valsartan during hospitalization may be associated with reduced hospitalizations, increased quality-adjusted life expectancy, and cost savings compared with no initiation or initiation after hospitalization.
Abstract: Importance Sacubitril-valsartan use reduces mortality and hospitalizations compared with enalapril among patients with chronic heart failure with reduced ejection fraction (HFrEF); however, the cost-effectiveness of these treatments when initiated during hospitalization for HF is unknown. Objective To estimate the cost-effectiveness of inpatient initiation of sacubitril-valsartan vs enalapril compared with no initiation or posthospitalization initiation of sacubitril-valsartan among stabilized patients with HFrEF. Design, Setting, and Participants This economic evaluation included data on US patients with HFrEF who were eligible for sacubitril-valsartan treatment from December 8, 2009, to May 15, 2018. Main Outcomes and Measures A 5-state Markov model with all-cause mortality, HF, and non-HF hospitalization probabilities was used. Quality of life was estimated using Euro-QoL EQ-5D scores. Hospitalization, long-term care, and medication costs for sacubitril-valsartan and enalapril were modeled with a discount rate of 3%. The base-case analysis included a lifetime horizon from a health care and societal perspective. Results Modeled patients were a mean (SD) age of 63.8 (11.5) years. Inpatient treatment with sacubitril-valsartan ($5628 per year) was associated with 62 fewer HF-related admissions per 1000 patients compared with outpatient initiation or 116 fewer HF-related admissions compared with continuation of enalapril treatment. From a health care system perspective, initiation of sacubitril-valsartan during hospitalization saved $452 per year compared with continuing enalapril and $811 per year compared with initiation at 2 months after hospitalization and was associated with an incremental cost-effectiveness ratio of $21 532 per quality-adjusted life-year compared with continued enalapril treatment over a lifetime. From a societal perspective, inpatient initiation was estimated to save $460 per year per patient compared with no initiation of sacubitril-valsartan and $813 per year per patient compared with initiation after hospitalization. In a budget analysis, inpatient initiation of sacubitril-valsartan was estimated to save up to $449 per person for 1 year or $2550 per person over 5 years compared with continuation of enalapril. Conclusions and Relevance The findings suggest that, for patients with HFrEF, initiation of sacubitril-valsartan during hospitalization may be associated with reduced hospitalizations, increased quality-adjusted life expectancy, and cost savings compared with no initiation or initiation after hospitalization.

45 citations


Journal ArticleDOI
TL;DR: The LIFE (LCZ696 In Hospitalized Advanced Heart FailurE) study is a 24-week prospective, multicenter, double-blinded, double dummy, active-comparator trial to assess the safety, efficacy and tolerability of S/V compared with V in patients with advanced HFrEF.
Abstract: The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Mor...

43 citations


Journal ArticleDOI
TL;DR: The preferred contemporary approach to the management of stable ischemic heart disease, also referred to as chronic coronary syndrome, is not well defined.
Abstract: The preferred contemporary approach to the management of stable ischemic heart disease, also referred to as chronic coronary syndrome,1 is not well defined. Two strategies are commonly used.2 The c...

Journal ArticleDOI
TL;DR: The findings of this cohort substudy suggest that a strategy incorporating hsTn into a guideline-derived ASCVD risk algorithm provides enhanced risk stratification and reclassifies 11.9% of patients into a more appropriate risk group.
Abstract: Importance The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol management guidelines identified 2 distinct groups of patients with atherosclerotic cardiovascular disease (ASCVD) prompting different treatment recommendations. Objective To investigate whether the addition of high-sensitivity troponin (hsTn) testing to guideline-derived ASCVD risk can improve risk classification and downstream treatment recommendations. Design, Setting, and Participants A prospective cohort biomarker substudy was performed that included 8635 patients enrolled in the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial. Patients were assigned to risk groups of either very high-risk ASCVD or lower-risk ASCVD based on their cardiovascular history and comorbidities, in line with the 2018 AHA/ACC cholesterol management guidelines criteria. Patients were also classified on the basis of hsTnI level (ARCHITECT assay; Abbott) using cut points of 2 ng/L (limit of detection) and 6 ng/L (risk threshold), followed by joint classification on the basis of clinical features and hsTnI level. The setting was a nested prospective cohort study in a completed multinational trial. Participants were all patients who had a myocardial infarction 1 to 3 years before enrollment, were at least 50 years of age, and had at least 1 high-risk feature. The study dates were October 2010 to December 2014. The dates of analysis were June 2019 to January 2020. Main Outcomes and Measures The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Results Among 8635 patients enrolled in the PEGASUS-TIMI 54 trial, the median age was 65 years (interquartile range, 58-71 years), and 6614 (76.6%) were men; 8340 (96.6%) were White individuals and 176 (2.0%) were Black individuals. Patients meeting clinical criteria for the very high-risk ASCVD group had a primary end point 3-year event rate of 8.8% compared with 5.0% in the lower-risk ASCVD group (hazard ratio, 2.01; 95% CI, 1.58-2.57;P Conclusions and Relevance The findings of this cohort substudy suggest that a strategy incorporating hsTn into a guideline-derived ASCVD risk algorithm provides enhanced risk stratification and reclassifies 11.9% of patients into a more appropriate risk group. This application of hsTn testing might be used to optimize the care of patients with ASCVD.

Journal ArticleDOI
TL;DR: Among patients admitted for acute decompensated HF, S/V was safe and well tolerated, led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide, and improved clinical outcomes compared with enalapril irrespective of previous HF history or ACE inhibitor or ARB treatment.

Journal ArticleDOI
TL;DR: Data from PEGASUS-TIMI 54 highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting.
Abstract: Aims PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup. Methods and results This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1-3years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15-1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68-0.99) and with prior stenting (HR 0.85, 95% CI 0.75-0.96; P for interaction = 0.76). Conclusion Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting.


Journal ArticleDOI
TL;DR: In patients undergoing PCI for ACS, spontaneous events predominate after 30 days, with the later-phase cardiovascular benefit of potent dual antiplatelet therapy driven largely by reducing de novo atherothrombotic ischemic events.

Journal ArticleDOI
TL;DR: Patients with diabetes in ENGAGE AF-TIMI 48 had higher bleeding risk, but after adjustment similar stroke risk, compared to those without diabetes, and the higher-dose edoxaban regimen had similar efficacy compared to warfarin, while reducing bleeding and cardiovascular mortality, irrespective of diabetes.

Journal ArticleDOI
TL;DR: Among Black patients admitted with ADHF in the United States, the in-hospital initiation of sacubitril/valsartan was more effective than enalapril in reducing natriuretic peptide levels and the composite of cardiovascular death or HF rehospitalization.
Abstract: Objectives This study compared the efficacy and safety of sacubitril/valsartan to enalapril in Black and non-Black Americans with acute decompensated heart failure (ADHF). Background Black patients have a different response to treatment with angiotensin-converting enzyme inhibitors compared with other racial and ethnic groups. How Black patients with ADHF respond to sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, is unclear. PIONEER-HF was a double-blind randomized clinical trial of sacubitril/valsartan versus enalapril in hospitalized patients with ADHF following hemodynamic stabilization. Methods In a pre-specified subgroup analysis, we examined changes in N-terminal pro–B-type natriuretic peptide, clinical outcomes, and safety according to race. Results The study population, all enrolled in the United States, included 316 (36%) Black participants, 515 (58%) White participants, and 50 (5.7%) participants of other racial groups. The reduction in N-terminal pro–B-type natriuretic peptide concentration at weeks 4 and 8 was significantly greater with sacubitril/valsartan than enalapril in both Black (ratio of change with sacubitril/valsartan vs. enalapril: 0.71; 95% confidence interval [CI]: 0.58 to 0.88) and non-Black patients (ratio of change: 0.71; 95% CI: 0.61 to 0.83; interaction p = 1.00). Compared with enalapril, sacubitril/valsartan also reduced the pre-specified exploratory composite of cardiovascular death or HF rehospitalization in both Black (hazard ratio: 0.47; 95% CI: 0.24 to 0.93) and non-Black patients (hazard ratio: 0.65; 95% CI: 0.40 to 1.06; interaction p = 0.44). Conclusions Among Black patients admitted with ADHF in the United States, the in-hospital initiation of sacubitril/valsartan was more effective than enalapril in reducing natriuretic peptide levels and the composite of cardiovascular death or HF rehospitalization. The effect of sacubitril/valsartan did not differ by race. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890)

Journal ArticleDOI
TL;DR: In hemodynamically stabilized patients with ADHF, the efficacy and safety of sacubitril/valsartan are generally consistent across dose levels.
Abstract: Objectives This study sought to evaluate the efficacy and safety of sacubitril/valsartan according to dose level achieved in the PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode) trial. Background In patients hospitalized for acute decompensated heart failure (ADHF), in-hospital initiation and continuation of sacubitril/valsartan as compared with enalapril is well tolerated, achieves a greater reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP), and reduces the risk of cardiovascular death or rehospitalization for HF through 8 weeks. However, not all patients achieve the target dose of sacubitril/valsartan, and its efficacy and safety in such patients are of interest. Methods PIONEER-HF was a randomized, double-blind, active-controlled trial of sacubitril/valsartan versus enalapril in 881 patients stabilized during hospitalization for ADHF. Blinded study medication was administered for 8 weeks, with initial dosing selected based on the systolic blood pressure at randomization and titrated toward a target of sacubitril/valsartan 97/103 mg twice daily, or enalapril 10 mg twice daily, with an algorithm based on systolic blood pressure and the investigator’s assessment of tolerability. Results At 4 weeks, 199 (55%) patients allocated to sacubitril/valsartan and 211 (60%) patients allocated to enalapril were dispensed the target dose. Baseline characteristics were similar in the 2 treatment groups within each dose level. There was no heterogeneity across dose levels in the effect of sacubitril/valsartan on the reduction in NT-proBNP (pinteraction = 0.69), the reduction in cardiovascular death or rehospitalization for heart failure (pinteraction = 0.42), or the pre-specified adverse events of special interest through 8 weeks. Conclusions In hemodynamically stabilized patients with ADHF, the efficacy and safety of sacubitril/valsartan are generally consistent across dose levels. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890)

Journal ArticleDOI
TL;DR: A previously derived and validated plasma Cer-PC risk score (CERT2) was associated with CV death risk in patients with stable disease, but its prognostic value has not been evaluated in patients early post-acute coronary syndrome (ACS) as mentioned in this paper.
Abstract: Aims Ceramide (Cer) and phosphatidylcholine (PC) lipids are associated with pathophysiological processes in cardiovascular (CV) diseases. A previously derived and validated plasma Cer-PC risk score (CERT2) was associated with CV death risk in patients with stable disease, but its prognostic value has not been evaluated in patients early post-acute coronary syndrome (ACS). Methods and results Prespecified plasma Cer and PC species of CERT2 risk score were measured in 4871 subjects from SOLID-TIMI 52, which enrolled patients ≤30 days after ACS (median follow-up 2.5 years). The CERT2 score (scale 0-12 points) was calculated as previously defined. The primary outcome was CV death; CV death or heart failure (HF) hospitalization (HF), myocardial infarction (MI), stroke, and all-cause death were also analysed. Poisson models included baseline characteristics and established biomarkers. Patients with higher CERT2 risk scores were more likely to be older, female, current smokers, presenting with STEMI, and to have impaired renal function and higher LDL-C. After multivariable adjustment, patients in the highest risk score category remained at a nearly two-fold higher risk of CV death (adj relative risk [RR] 1.92, 95% CI 1.01-3.66, P = 0.047). Patients in the highest risk score category were also at higher risk of all-cause death (adj RR 2.01, 95% CI 1.21-3.35, P = 0.007), whereas the relationships with HF, MI, and stroke were attenuated with multivariable adjustment. Conclusions A plasma ceramide and phospholipid-based risk score are associated with the risk of CV death independent of established clinical risk factors and biomarkers in patients after ACS.

Journal ArticleDOI
05 Feb 2020
TL;DR: This cohort study investigates the association of hypertrophic obstructive cardiomyopathy with outcomes following transcatheter aortic valve replacement.
Abstract: This cohort study investigates the association of hypertrophic obstructive cardiomyopathy with outcomes following transcatheter aortic valve replacement.

Journal Article
TL;DR: The subject of this paper is a man who lived for 21 years with this malformation, which was a complete transposition of the great vessels in infancy.
Abstract: Excerpt The majority of patients with complete transposition of the great vessels die in infancy. The subject of this paper is a man who lived for 21 years with this malformation, which was associa...

Journal ArticleDOI
01 Sep 2020
TL;DR: A prospective systematic analysis of malignancy events in IMPROVE-IT, where patients randomized to either ezetimibe 10 mg or matching placebo on a background of simvastatin 40 mg who took ≥1 dose of the study drug had a similar incidence of malignant events compared with those receiving placebo during a median follow-up of 6 years.
Abstract: Background An increased risk of malignancy was reported with simvastatin/ezetimibe in 1,873 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial. Objectives The purpos...

Journal ArticleDOI
TL;DR: Edoxaban 60 mg (30 mg dose-reduced) was associated with a significantly lower overall rate of cardiovascular- or bleeding-related hospitalization and significant reductions in the subcategories of cardiovascular, related, stroke-related, bleed- related, and nonstroke cardiovascular–related hospitalizations, when compared with warfarin, suggesting the potential for cost offsets with edoxaban.
Abstract: Background The ENGAGE AF–TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) demonstrated noninferiority of once...

Journal ArticleDOI
TL;DR: A higher WBC count at baseline was associated with an increased risk of the composite bleeding endpoint by 30 days but not at 1 year, and the association between W BC count and the risk of a composite ischemic endpoint was significant at 30 days and 1 year.
Abstract: An elevated white blood cell (WBC) count is associated with an increased risk of ischemic events among acute coronary syndrome (ACS) patients, but the association between WBC count and bleeding in ACS patients is not well established. The aim of this analysis was to assess and compare the association between WBC count and the occurrence of short- and long-term bleeding and ischemic events. This was a post hoc analysis of the ATLAS ACS2-TIMI 51 trial. A subset of patients had a WBC count measurement at baseline (n = 14,231, 91.6%). Univariate and multivariable Cox proportional hazard models were constructed to determine if there is an association between WBC count at baseline and a composite outcome of Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeds at 30 days and 1 year. Variables with a p